Composition and methods for controlling coccidiosis in poultry



United States Patent ABSTRACT OF THE DISCLOSURE Anticoccidial and growth-promoting compositions comprising 4-sulfanilamido-2,6-dirnethoxypyrimidine and 2,4- dianiino--( 3 ,4-dimethoxybenzyl pyrimidine.

CROSS-REFERENCE TO RELATED APPLICATION This application is a continuation-in-part of Ser. No. 473,485, filed July 20, 1965, now abandoned.

BACKGROUND OF THE INVENTION In poultry, coccidiosis is a very widespread disease which occurs in the form of severe intestinal infections and often proves fatal. This disease is produced by infection with protozoa of the genus Eimeria such as, for example, Eimeria tenella. The compositions in accordance with the invention make possible successful control of coccidiosis by preventing checking and/or curing said disease. Control of the disease is accomplished by administering the composition of the invention to poultry (e.g., hens or turkey cocks) in effective quantities. They also exert a growth-promoting action in poultry and accordingly, are also useful as growth-promoting agents.

SUMMARY OF THE INVENTION The anticoccidial and growth-promoting compositions in accordance with the invention contain (a) a physiologically acceptable carrier material, e.g., solid or liquid poultry feed or drinking water, (b) 4-sulfanilamido-2,6- dimethoxypyrimidine (hereinafter referred to as Compound I) or a salt thereof with a pharmaceutically acceptable base, and (c) 2,4-diamino-5-(3,4-dimethoxybenzyl) pyrimidine (hereinafter referred to as Compound II) or a salt thereof with a pharmaceutically acceptable acid.

DETAILED DESCRIPTION OF THE INVENTION The anticoccidial and growth-promoting compositions of the invention contain (a) a physiologically acceptable carrier material, e.g., solid or liquid poultry feed or drinking water, (b) 4-sulfanilamido-2,6-dimethoxypyrimidine (hereinafter referred to as Compound I) or a salt thereof with a pharmaceutically acceptable base, and (c) 2,4-diamino-S-(3,4-dimethoxybenzyl) pyrimidine (hereinafter referred to as Compound II) or a salt thereof with a pharmaceutically acceptable acid. The compositions of the invention control coccidiosis by preventing, checking and/ or curing the disease.

The compositions of the invention are prepared by mixing Compounds I and II in uniform and finely divided form in a liquid or solid feed, or dispersing them in poultry drinking water. Standard commercial poultry feed products can be used as the liquid or solid feed. Additionally, other compositions containing ingredients suitable for poultry nutrition can also be employed such as animal feed products. For controlling coccidiosis in poul try, the instant compositions contain between about 0.010 and about 0.050 Weight percent, preferably about 0.0125

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and about 0.0250 weight percent, of a mixture of Compounds I and II, wherein Compound II is present in from about 5 to about 30, preferably about 15 to about 30 weight percent of the total weight of the mixture of Compounds I and II. For producing a promotion of growth, the instant composition contains between about 0.006 and about 00125 weight percent, of a mixture of Compounds I and II, wherein Compound II is present in from about 5 to about 30, preferably about 15 to about 30 weight percent of the total weight of the mixture of Compounds I and II. In special cases it may be convenient to use concentrations which are smaller or larger than the values named above.

A uniform distribution of Compounds I and II in the carrier material can easily be effected according to the usual methods, by mixing, grinding, stirring, or with solid feed, spraying dilute solutions (preferably in water) of Compounds I and II onto feed. Both Compounds I and II are only water soluble in the form of their salts. Therefore, for the manufacture of aqueous preparations, salts must be employed or an aqueous dispersion must be prepared using the usual emulsifiers. The alkali metal salts such as the sodium or potassium salt are especially suitable as salts of Compound I. Compound II forms acid addition salts with pharmaeeutically acceptable acids, e.g., mineral acids such as hydrochloric, hydrobromic, sulfuric, phosphoric, nitric, etc, organic acids, such as acetic, benzenesulfonic, toluenesulfonic, etc., which can be used for this purpose. As emulsifiers, the nonionic emulsifiers are preferred, e.g., polyoxyethylene sorbitan monooleate or laurate or polyoxyethylene ricinoleate, etc.

When a feed in which the mixture of Compounds I and II have been incorporated in accordance with the invention is administered to poultry, an undisturbed feed uptake is observed, even after infection with sporulated oocysts. The general condition of the poultry remains unaltered and no clinical manifestation is observed.

In another embodiment of the invention, Compounds I and II can also be utilized in compositions in the form of concentrates which then, as additives, are diluted with the basic feed prior to feeding. The compositions in the form of concentrates contain the above mixture of Compound I and II in concentrations of about 5 to about weight percent, preferably about 10 to about 25 weight percent of the weight of concentrate, the remainder being a physiologically acceptable carrier material, such as those employed above, or one or more of the following: grain, side products of the milling industry, ground oil cake, distillation residues of the fermentation industry, finely divided mineral materials, ground oyster shells, silicon dioxide, etc. Fats, oils antioxidants and surface active ma terials can also be employed as the carrier material for these concentrates.

In addition to Compounds I and II, other preparations of veterinary-medicinal activity can be added to the compositions of the invention.

Example 1 Groups of ten, weighed, two-Week-old chicks, were fed with a feed containing for each kg. of feed, 60 or mg. of a mixture of 4-sulfanilamido-2,G-dimethoxypyrimidine (80 weight percent) and 2,4-diamino-5-(3,4-dirnethoxybenzyl)pyrimidine (20 weight percent). 72 hours after starting the feeding of the above feed, each chick was infected per os with 100,000 sporulated oocysts of Ez'meria tenella.

Control groups, each of ten, Weighed, two-Week-old chicks, were fed with the same feed to which, however, none of the above mixture of compounds was added, and were each likewise infected per os with 100,000 sporulated oocysts. After an experiment duration of eight days,

3 the chicks which were still alive, from both the test and control groups were killed, weighed, and examined for pathological changes. The results were compiled in the following table:

Mixture of 4-sultanila1nido- By strong is meant severe damage of the epithelium with heavy bleedings. By very slight is meant slightly damaged epithelium accompanied by single bleedings.

Analogous results were obtained when the above mixclaim 1, wherein 2,4-diamino-5-(3,4-dimethoxybenzyl) pyrimidine or a salt thereof with a pharmaceutically acceptable acid is present in from about 15 to about 30 percent by weight of the weight of the mixture.

3. A composition for controlling coccidiosis in poultry which comprises:

(a) a physiologically acceptable carrier material; (b) 4-sulfanilamido-2,6-dirnethoxypyrimidine or a salt thereof with a pharmaceutically acceptable base; and (c) 2,4-diamino-5-(3,4 dimethoxybenzyl)pyrimidine or a salt thereof with a pharmaceutically acceptable acid wherein the above composition contains from about 0.0125 to about 0.0250 percent by weight of a mixture of (b) and (c) wherein compound is present in from 15 ture f 4-SulfaI111flm1d0- dlmethoxypyrmudme and about to about 30 percent by Weight of the weight of 2,4-diamino-5-(3,4-dimethoxybenzyl)pyrimidine Was mthe mixture of (b) and (c). ployed in a ratio of 70:30 W ight percent rat r than 4. An anticoccidial composition in accordance with 80:20 weight percent as above. claim 3, wherein 2,4-diamin0-5-(3,4-dimethoxybenzyl) E I 2 2O pyrimidine or a salt thereof with a 'pharmaceutically ac- Xamp e ceptable acid is present in from about to about 30 per- The synergistic action of the compositions of this invencent by Weight of the weight of the mixture of (b) tion in controlling coccidiosis in poultry was demonstrated and (c). as follows: 5. A method for controlling coccidiosis in poultry,

Ten chickens approximately three weeks old per group which comprises administering to said poultry an effecwere employed for each drug group as a non-infected tive amount of a composition comprising 4-sulfanilamidoweight control group and as an infected control group. 2,6-dimethoxy pyrimidine or a salt thereof with a phar- The drug was given orally by diet 72 hours in advance maceutically acceptable base and 2,4-diamino-5-(3,4- of the infection at dosage levels as indicated. The infecdirnethoxybenzyl) pyrimidine or a salt thereof with a tion consisted of approximately 125,000 oocysts of pharmaceutically acceptable acid wherein the 2,4-di- E. tenella given orally. The stools were observed for amino-5-(3,4-dimethoxybenzyl)pyrimidine is present in clinical symptoms of intestinal hemorrhaging four and from about 5 to about 30 percent by weight of the weight five days after infection. The severity of lesions in the of the mixture. intestinal tract is indicated by observing the amount of 6. A method in accordance with claim 5, wherein blood present in the tools and rated as follows: 2,4-diamino-5-(3,4-dimethoxybenzyl)pyrimidine or a salt thereof with a pharmaceutically acceptable acid is present fi$iffi in from about 15 to about 30 percent by weight of the weight of the mixture. +1=blood present occasionally 7 A method of controlling coccidlosis in poultry +2 moderate amount of blood amount of blood 40 which comprises administering to said poultry an effecvy tive amount of a composition comprising: The results obtained when compound A and compound (a) a physiologically acceptable carrier material; B were administered singly and in combination according (b) 4-sulfanilamido-2,6-dimethoxypyrimidine or a salt to the procedure described above were as follows: thereof with a pharmaceutically acceptable base;

E. tenella 1 E. tenella 3 Compound Dose (weightgpercent Blood in Stools Blood in Stools 4 days after 5 days after 4 days after 5 days after infection infection infection infection 0 +2 +2 +2 +2 +1 +2 +1 +2 +2 +2 +2 +2 +2 +2 +2 +2 +3 +3 4 4 4 Q d n+3 307 B) 0175 A-l- 0075 B i Z Z i 0 :00S75 A-la00375 'B'II o Unintected, Untreated Control. Infected. Untreated +3 Control.

1 HLR Hoechst strain of E. tcnella.

I claim:

1. A composition for controlling coccidiosis in poultry, which comprises 4-sulfanilamido-2,6-dimethoxy pyrimidine or a salt thereof with a pharmaceutically acceptable base and 2,4-diamino-5-(3,4-dimethoxybenzyl)pyrimidine or a salt thereof with a pharmaceutically acceptable acid wherein 2,4-diamino-5- 3 ,4dime'thoxybenzyl pyrimidine or a salt thereof with a pharmaceutically acceptable acid is present in from about 5 to about 30 percent by weight of the weight of the mixture;

2 HLR ARD strain of E. tenella.

2. An anticoccidial composition in accordance with and (c) 2,4-diamino-5-(3,4 dimethoxybenzyl)pyrimidine or a salt thereof with a pharmaceutically acceptable acid wherein the above composition contains from about 0.0125 to about 0.0250 percent by weight of a mixture of (b) and (c) wherein compound (c) is present in from about 5 to about 30 percent by weight of the weight of the mixture of (b) and (c).

8. A method in accordance with claim 7, wherein 2,4-diamino-5-(3,4-dirnethoxybenzyl) pyrimidine or a salt thereof with a pharmaceulically accepiable acid is present OTHER REFERENCES in from about 15 to about 30 percent by weight of the Tsunda V6261. Bun. vol 34 (1964) page weight of the mixture of (b) and (c).

ALBERT T. MEYERS, Primary Examiner.

References Cited 5 S. J. FRIEDMAN, Assistant Examiner.

UNITED STATES PATENTS 2,823,160 2/1958 Lux 167-531 

